Engineered exosomes derived from stem cells: a new brain-targeted strategy

ABSTRACT

Introduction

Using engineered exosomes produced from stem cells is an experimental therapeutic approach for treating brain diseases. According to reports, preclinical research has demonstrated notable neurogenesis and angiogenesis effects using modified stem cell-derived exosomes. These biological nanoparticles have a variety of anti-apoptotic, anti-inflammatory, and antioxidant properties that make them very promising for treating nervous system disorders.

Areas covered

This review examines different ways to enhance the delivery of modified stem cell-derived exosomes, how they infiltrate the blood-brain barrier (BBB), and how they facilitate their access to the brain. We would also like to determine whether these nanoparticles have the most significant transmission rates through BBB when targeting brain lesions.

Expert opinion

Using engineered stem cell-derived exosomes for treating brain disorders has generated considerable attention toward clinical research and application. However, stem cell-derived exosomes lack consistency, and their mechanisms of action are uncertain. Therefore, upcoming research needs to prioritize examining the underlying mechanisms and strategies via which these nanoparticles combat neurological disorders.

KEYWORDS:

• Stem cells
• exosomes
• BBB
• CNS
• engineered

Article highlights

• Stem cell-derived exosomes (SCEs) have been shown to significantly affect the regulation of several biological processes and encourage neurogenesis.

• SCEs have been shown to increase the permeability of brain endothelial cells (ECs) during inflammation by modifying the control of tight junctions (TJs) via occludin and claudins.

• SCEs can be loaded with or modified with therapeutic proteins to pass the BBB and target cerebral diseases.

• SCE engineering can increase the targeting rate and decrease the required dosage, which may be crucial to their clinical application.

• SCEs have therapeutic properties like parent cells but avoid adverse events, pass barriers, migrate to brain lesions, and have a high safety profile without immune response or rejection.

Abbreviations

SCEs	=	Stem cell-derived exosomes
BBB	=	Blood-brain barrier
CNS	=	Central nervous system
ECs	=	Endothelial cells
TJs	=	Tight junctions
TfR	=	Transferrin receptor
DNA	=	Deoxyribonucleic acid
RNA	=	Ribonucleic acid
ESCs	=	Embryonic stem cells
MSCs	=	Mesenchymal stem cells
iPSCs	=	pluripotent stem cells
BM-MSC	=	Bone marrow-derived mesenchymal stem cell
BCEC	=	Brain capillary endothelial cells
CSF	=	Cerebrospinal fluid
MVB	=	Multivesicular body
ECM	=	Extracellular matrix

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

This work was partially sponsored by the National Key R&D Program of China [2022YFA1104900 and 2022YFA1104904], Innovation team project of general universities in Guangdong province [2023KCXTD007], the Natural Science Foundation of Guangdong Province [2021A1515010013], the Department of Education of Guangdong Province [2021ZDZX2011], the Guangzhou Municipal Science and Technology Project [202201011760], and the President Foundation of the Integrated Hospital of Traditional Chinese Medicine of Southern Medical University [1202101003].